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Identification
NamePomalidomide
Accession NumberDB08910
TypeSmall Molecule
GroupsApproved
Description

Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • CC-4047
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pomalystcapsule1 mg/1oralCelgene Corporation2013-02-18Not applicableUs
Pomalystcapsule4 mgoralCelgene Inc2014-02-24Not applicableCanada
Pomalystcapsule3 mgoralCelgene Inc2014-02-24Not applicableCanada
Pomalystcapsule2 mgoralCelgene Inc2014-02-24Not applicableCanada
Pomalystcapsule1 mgoralCelgene Inc2014-02-24Not applicableCanada
Pomalystcapsule4 mg/1oralCelgene Corporation2013-02-18Not applicableUs
Pomalystcapsule3 mg/1oralCelgene Corporation2013-02-18Not applicableUs
Pomalystcapsule2 mg/1oralCelgene Corporation2013-02-18Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ImnovidNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIID2UX06XLB5
CAS number19171-19-8
WeightAverage: 273.2441
Monoisotopic: 273.074955855
Chemical FormulaC13H11N3O4
InChI KeyInChIKey=UVSMNLNDYGZFPF-UHFFFAOYNA-N
InChI
InChI=1/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)
IUPAC Name
4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
SMILES
NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O
Taxonomy
ClassificationNot classified
Pharmacology
IndicationPomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.
PharmacodynamicsPomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times).
Mechanism of actionPromalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2.
Related Articles
AbsorptionPomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses.
Volume of distribution

Mean apparent volume of distribution (Vd/F), steady-state = 62 – 138 L

Protein binding12-44% protein bound. It is not concentration dependent.
Metabolism

Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro.

Route of eliminationWhen a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively.
Half lifeHealthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours.
Clearance

Total body clearance = 7-10 L/hour

ToxicityMost common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9653
Blood Brain Barrier+0.8304
Caco-2 permeable-0.6419
P-glycoprotein substrateSubstrate0.5264
P-glycoprotein inhibitor INon-inhibitor0.5983
P-glycoprotein inhibitor IINon-inhibitor0.9147
Renal organic cation transporterNon-inhibitor0.847
CYP450 2C9 substrateNon-substrate0.844
CYP450 2D6 substrateNon-substrate0.8882
CYP450 3A4 substrateSubstrate0.5079
CYP450 1A2 substrateNon-inhibitor0.8863
CYP450 2C9 inhibitorNon-inhibitor0.8428
CYP450 2D6 inhibitorNon-inhibitor0.9002
CYP450 2C19 inhibitorNon-inhibitor0.8513
CYP450 3A4 inhibitorNon-inhibitor0.7289
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8686
Ames testNon AMES toxic0.7979
CarcinogenicityNon-carcinogens0.9081
BiodegradationNot ready biodegradable0.9858
Rat acute toxicity2.5862 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9885
hERG inhibition (predictor II)Non-inhibitor0.7765
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral1 mg/1
Capsuleoral1 mg
Capsuleoral2 mg
Capsuleoral2 mg/1
Capsuleoral3 mg
Capsuleoral3 mg/1
Capsuleoral4 mg
Capsuleoral4 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5635517 No1996-07-242016-07-24Us
US6045501 No1998-08-282018-08-28Us
US6315720 No2000-10-232020-10-23Us
US6316471 No1996-08-102016-08-10Us
US6476052 No1996-07-242016-07-24Us
US6561976 No1998-08-282018-08-28Us
US6561977 No2000-10-232020-10-23Us
US6755784 No2000-10-232020-10-23Us
US6908432 No1998-08-282018-08-28Us
US8158653 No1996-08-102016-08-10Us
US8198262 No2004-10-192024-10-19Us
US8204763 No1998-08-282018-08-28Us
US8315886 No2000-10-232020-10-23Us
US8589188 No1998-08-282018-08-28Us
US8626531 No2000-10-232020-10-23Us
US8673939 No2003-05-152023-05-15Us
US8735428 No2003-05-152023-05-15Us
US8828427 No2011-06-212031-06-21Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility2.57 mg/mLALOGPS
logP0.02ALOGPS
logP-0.16ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)11.59ChemAxon
pKa (Strongest Basic)1.56ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.57 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity69.03 m3·mol-1ChemAxon
Polarizability25.81 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [PubMed:22917017 ]
  2. McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [PubMed:23730498 ]
  3. Terpos E, Kanellias N, Christoulas D, Kastritis E, Dimopoulos MA: Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. Onco Targets Ther. 2013 May 10;6:531-8. doi: 10.2147/OTT.S34498. Print 2013. [PubMed:23690693 ]
External Links
ATC CodesL04AX06
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (292 KB)
MSDSDownload (479 KB)
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Abatacept.
AbirateroneThe serum concentration of Pomalidomide can be increased when it is combined with Abiraterone.
AnakinraThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Anakinra.
AzelastinePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Pomalidomide.
BortezomibThe metabolism of Pomalidomide can be decreased when combined with Bortezomib.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
BuprenorphinePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CanakinumabThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Canakinumab.
CarbamazepineThe metabolism of Pomalidomide can be increased when combined with Carbamazepine.
Certolizumab pegolPomalidomide may increase the immunosuppressive activities of Certolizumab pegol.
CiprofloxacinThe serum concentration of Pomalidomide can be increased when it is combined with Ciprofloxacin.
ClozapineThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Clozapine.
Cyproterone acetateThe serum concentration of Pomalidomide can be decreased when it is combined with Cyproterone acetate.
DeferasiroxThe serum concentration of Pomalidomide can be increased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Pomalidomide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
EthanolPomalidomide may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
FluvoxamineThe serum concentration of Pomalidomide can be increased when it is combined with Fluvoxamine.
HydrocodonePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
LeflunomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Leflunomide.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Pomalidomide.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Pomalidomide.
MethotrimeprazinePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MethoxsalenThe serum concentration of Pomalidomide can be increased when it is combined with Methoxsalen.
MetyrosinePomalidomide may increase the sedative activities of Metyrosine.
MexiletineThe serum concentration of Pomalidomide can be increased when it is combined with Mexiletine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
MirtazapinePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
NatalizumabThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Natalizumab.
OfloxacinThe serum concentration of Pomalidomide can be increased when it is combined with Ofloxacin.
OrphenadrinePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
PamidronateThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Pamidronate.
ParaldehydePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Paroxetine.
Peginterferon alfa-2bThe serum concentration of Pomalidomide can be increased when it is combined with Peginterferon alfa-2b.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pomalidomide.
PramipexolePomalidomide may increase the sedative activities of Pramipexole.
PrimaquineThe serum concentration of Pomalidomide can be increased when it is combined with Primaquine.
RilonaceptThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Rilonacept.
RoflumilastRoflumilast may increase the immunosuppressive activities of Pomalidomide.
RopinirolePomalidomide may increase the sedative activities of Ropinirole.
RotigotinePomalidomide may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Pomalidomide.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pomalidomide.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
StiripentolThe serum concentration of Pomalidomide can be increased when it is combined with Stiripentol.
SuvorexantPomalidomide may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pomalidomide.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Pomalidomide.
TeriflunomideThe serum concentration of Pomalidomide can be decreased when it is combined with Teriflunomide.
ThalidomidePomalidomide may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TocilizumabTocilizumab may increase the immunosuppressive activities of Pomalidomide.
TofacitinibThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Pomalidomide.
VedolizumabThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Vedolizumab.
VemurafenibThe serum concentration of Pomalidomide can be increased when it is combined with Vemurafenib.
ZolpidemPomalidomide may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly an...
Gene Name:
CRBN
Uniprot ID:
Q96SW2
Molecular Weight:
50545.375 Da
References
  1. McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [PubMed:23730498 ]
  2. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H: Identification of a primary target of thalidomide teratogenicity. Science. 2010 Mar 12;327(5971):1345-50. doi: 10.1126/science.1177319. [PubMed:20223979 ]
  3. Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R: Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. [PubMed:22552008 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Tumor necrosis factor receptor binding
Specific Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
Gene Name:
TNF
Uniprot ID:
P01375
Molecular Weight:
25644.15 Da
References
  1. Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [PubMed:22917017 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Ferguson GD, Jensen-Pergakes K, Wilkey C, Jhaveri U, Richard N, Verhelle D, De Parseval LM, Corral LG, Xie W, Morris CL, Brady H, Chan K: Immunomodulatory drug CC-4047 is a cell-type and stimulus-selective transcriptional inhibitor of cyclooxygenase 2. J Clin Immunol. 2007 Mar;27(2):210-20. Epub 2007 Feb 17. [PubMed:17308870 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Comments
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Drug created on June 20, 2013 16:45 / Updated on July 01, 2016 01:52